(507a) JNK Regulates Adherens Junctions by Phosphorylating Beta-Catenin

Cell-cell adhesion is dynamically regulated under different biological circumstances such as the establishment of epithelial cell polarity, wound healing, cell scattering and tumorigenesis. However, the mechanism of adherens junction regulation is not completely understood. The current work led to the discovery that the well known kinase, c-Jun N-terminal kinase (JNK) is associated with adherens junctions and regulates cell-cell adhesion.

Specifically, we found that blocking JNK led to translocation of E-cadherin and beta-catenin to the cell surface and formation of compact colonies, suggesting a possible role of JNK in cell adhesion. Indeed, immunostaining and co-immunoprecipitated showed that JNK co-localized and bound to adherens junctions (AJs) complexes. In vitro kinase assays and mass spectrometry determined that JNK phosphorylated beta-catenin at serine 33/37 and threonine 41. Surprisingly, these were the same sites phosphorylated by GSK3-beta, which is involved in beta-catenin transcriptional activity. In addition, a combination of chemical inhibitors, dominant negative JNK constructs and siRNA indicated that JNK binds to and phosphorylated beta-catenin and that this phosphorylation leads to dissolution of adherens junctions and cell scattering. Our results showed for the first time that JNK is involved in regulation of adherens junctions by binding to and phosphorylating beta-catenin. These findings contribute to our understanding of cell-cell adhesion and may have wider implications in wound healing, embryonic development, tissue engineering and cancer metastasis.